Monday, May 11, 2015

Mutagenesis Induction in Viruses

Viruses - particularly retroviruses like HIV - are notorious for their ability to mutate. The rapid replication of viruses paired with their high mutation rate allow viruses to adapt to their host quickly. However, mutations are only beneficial to a certain extent, and most mutations are likely maladaptive. Using this information, scientists at the University of Chicago and MIT have been able to induce mutagenesis in viruses, increasing their rate of mutation to a point where the virus can no longer function effectively. Moreover, these scientists have developed a spectroscopy method that further elucidates the mechanism behind nucleotide analogs.

The researchers used an anti-HIV agent called KP1212 that evades viral detection and infiltrates a viruses genome. KP1212 functions essentially as a nucleotide analog that mimic DNA bases and result in mismatching of the normal adenosine-thymine, and cytosine-guanine base pairings in DNA. KP1212 is believed to work by repositioning hydrogen atoms in DNA, and resulting in faulty hydrogen bonding.

The use of two-dimensional infrared microscopy by the scientists to examine the structure of mutated viral DNA is novel, as scientists typically use nuclear magnetic resonance. The benefit of infrared microscopy is that scientists can examine the quickly changing structures of mutagenic viral DNA in aqueous solution (the natural environment of cells) as opposed to organic solvents. The ability of infrared microscopy to detect different mutagenic viral DNA structures, which quickly change shape and are keenly sensitive to time-changes, has resulted in the discovery of many different tautomers invoked by the KP1212 molecule.